Relation of the group Mathematical Cell Physiology to BIMSB
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Dr. Martin Falcke
31.2: Max-Delbrück Haus (Flachbau)
Raum: 0213
Tel. 9406-2753
Function is dynamics and the Berlin Institute for Medical Systems Biology will use the output of high throughput methods for representing cells as dynamic systems. Indeed, this is one of its appealing and ambitious goals. Our interest is dynamic modeling. Another task of BIMSB is to analyze genetic variability on DNA, RNA and protein level and to link it to function and behavior. Surprisingly, despite a large variety of protein concentrations, cells of a specific type are able to execute identical functions. Dynamic theory provides the framework for understanding the relation between plasticity, variability and function. The analog to function in the theory of dynamic systems is a dynamic regime. The mathematical structure allowing to asses genetic variability on a functional level is bifurcation theory. It determines conservation of function or its loss due to genetic variability by outlining the boundary of dynamic regimes (functions) in terms of expression levels, RNA concentrations and other parameter values characterizing cellular systems.
The group Mathematical Cell Physiology at the Max Delbrück Centre focuses on dynamic modeling and bifurcation theory, stochastic theory and spatio-temporal structures. We comprehend modeling as the quantitative formulation of biological hypotheses. The group has expertise in problem-oriented model development, mechanistic modeling and data analysis with respect to modeling. Model development comprises design of a first model based on the experimental state of the art, identification of crucial questions which can be addressed experimentally, corresponding experiments and model refinement (specification of the hypothesis). With our experimental partners, we usually go several times through that circle with the goal to clearly define experimental mechanisms.
The group has expertise in modeling of cell signaling pathways, spatio-temporal (intra- and intercellular) systems and cell mechanics. We have applied that expertise to Ca2+ and cAMP signaling in a variety of cell types including astrocytes and cardiac myocytes, neuronal modeling, modeling of cell motility and lamellipodium dynamics. Modeling in the group is moving towards more and more complex pathways like e.g. EGF receptor signaling. These applications establish the link to the BIMSB focus on neurodegenerative diseases and cancer.
We offer expertise in the use of modeling tools like copasi or Virtual Cell. These tools are especially eligible for analysis of large systems with many components. We apply them e.g. to the interaction of pH regulation, water transport, cAMP and Ca2+ signaling in salivary gland. At the same time, we develop spatially resolved cell models and modeling tools for applications which can not be handled by standard software. These methods are required for all modeling efforts requiring subcellular detail.
We have developed multi-scale modeling concepts which start from state changes of individual molecules and go up to dynamics on cell level. These methods can account for subcellular structures and compartmentalization of cells by concentration gradients. At the same time we use rate equations and methods with concentrations averaged across the cell volume for modeling pathways and slow systems.
link to the research group of Dr. Martin Falcke